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Aims: Data regarding expression of intestinal markers in hepatocellular carcinoma (HCC) are limited. We determined the clinicopathological associations of cytokeratin (CK)19, a progenitor liver epithelial cell marker as well as biliary epithelial marker, and intestinal immunohistochemical markers expression in HCC and assessed their prognostic value., Methods and Results: Tissue sections and/or tissue microarrays (TMAs) from 202 known HCCs were immunostained using CK19, CK20, CDH17, CDX2 and SATB2 antibodies. Haematoxylin and eosin (H&E)-stained slides were reviewed for tumour grading. Clinical and oncological outcomes were retrieved. Associations of staining with clinicopathological features and survival outcomes were evaluated. CK19, CK20, CDH17, CDX2 and SATB2 were positive in 12.8, 5.4, 10.3, 8.6 and 59.9%, respectively. All but SATB2 were strongly associated with higher tumour grade and AFP levels > 400 ng/ml (P < 0.05). CK19-positive HCC were more likely to express CDX2 (P = 0.001), CDH17 (P < 0.001) and/or CK20 (P = 0.012). CK20, CDX2 and CDH17 co-expression was seen in five cases (2.5%). CK19 and SATB2 positivity, tumour size ≥ 5 cm, background cirrhosis, AFP > 400 ng/ml and having no treatment were associated with decreased overall survival by log-rank test and univariable proportional hazards regression. However, in a multivariable model, CK19 and SATB2 positivity were not independent predictors of decreased survival while their association with known poor prognosticators in HCC was evident., Conclusions: HCC can express markers of intestinal differentiation. This phenotypical aberrancy correlates with variable clinicopathological parameters, some of which are independent predictors of poor survival., (© 2021 John Wiley & Sons Ltd.)

Background: As one of the leading cancer-related mortalities worldwide, colorectal cancer (CRC) shows resistance to chemotherapy mainly because of drug resistance. Existing evidence has revealed that long noncoding RNAs (lncRNAs) are related to tumorigenesis and chemoresistance scenarios. However, the mechanism by which lncRNA induces chemoresistance and the postoperative prognosis of CRC both remain unclear., Methods: The expression of a lncRNA named lncARSR in CRC tissue was tested, and its association with clinical and pathological features was analyzed. Gain-of-function and loss-of-function assays were conducted to investigate the role of lncARSR in vivo and in vitro., Results: Functional analysis showed that overexpressing lncARSR increased oxaliplatin (OXA) resistance of CRC cells in vitro and in vivo. Moreover, lncARSR conferred chemoresistance to CRC cells. Silencing lncARSR decreased cell viability and promoted cell apoptosis after OXA treatment, whereas overexpression of lncARSR increased cell viability and reduced cell apoptosis after OXA treatment. In addition, lncARSR overexpression induced the tumor formation capacity of colorectal cancer cells., Conclusions: The results obtained in the present study show that up-regulation of lncARSR promoted OXA resistance in CRC. Our results also imply that lncARSR may be a candidate marker for CRC chemoresistance., (© 2020 John Wiley & Sons, Ltd.)

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with a poor survival outcome. Predicting patient survival allows physicians to tailor treatments to specific individuals. Thus, a simple and cost-effective prognosis model is sorely needed. Methods: This retrospective study assesses the prognostic value of blood biomarkers in advanced and metastatic PDAC patients (n=96) from Spain. Cut-off points for hematological parameters were calculated and correlated with overall survival (OS) using Kaplan-Meier, log-rank test, robust Cox proportional hazards and logistic regressions. Results: In univariate analysis, individuals with low levels of GGT, LDH, ALP, leukocyte-, neutrophil- and monocyte counts showed significantly longer survival than patients with higher levels. In multivariate analysis, lower levels of GGT (HR (95%CI), 2.734 (1.223-6.111); p=0.014), LDH (HR (95%CI), 1.876 (1.035-3.400); p=0.038) and monocyte count (HR (95%CI), 1.657 (1.095-2.506); p = 0.017) remained significantly beneficial. In consequence, we propose a prognostic model based on logistic regression (AUC=0.741) of these three biomarkers as a pioneer tool to estimate OS in PDAC. Conclusion: This study has demonstrated that the joint use of GGT (<92.00), LDH (<220.00) and monocyte count (<800) are independent positive prognostic factors in PDAC that can predict one-year survival in a novel prognostic logistic model. [ABSTRACT FROM AUTHOR]

Background: This study aimed to compare the survival outcomes of transarterial chemoembolization (TACE) between patients with early recurrent hepatocellular carcinoma (rHCC) after hepatic resection, stratified by cytokeratin (CK) 19 expression. Methods: A retrospective analysis was conducted on 63 patients with early rHCC after hepatic resection who underwent TACE between January 2017 and December 2021. Patients were divided into two groups based on CK19 expression: CK19-negative (n=31) and CK19-positive (n=32). Overall survival (OS) and progression-free survival (PFS) were compared between the two groups using the Kaplan-Meier method and log-rank test. Cox regression analysis was performed to identify independent risk factors for OS and PFS. Results: The CK19-negative group demonstrated a significantly longer median OS compared to the CK19-positive group (635 days vs. 432 days, p=0.013). Similarly, the CK19-negative group had a longer median PFS than the CK19-positive group (291 days vs. 117 days, p=0.014). Multivariate Cox analysis identified Child-Pugh A grade, CK19-negative expression, and increased TACE sessions as protective factors for OS. No severe TACE-related adverse events were observed. Conclusion: In patients with early rHCC after hepatic resection, those with CK19-positive expression had poorer survival outcomes following TACE compared to CK19-negative patients. These findings suggest the need for additional therapies to improve survival in CK19-positive individuals. [ABSTRACT FROM AUTHOR]

Background: Non‐small‐cell lung cancer (NSCLC) often presents at later stages, typically associated with poor prognosis. Autophagy genes play a role in the progression of tumors. This study investigated the clinical relevance, prognostic value, and biological significance of RBBP4 in NSCLC. Methods: We assessed RBBP4 expression using the GSE30219 and TCGA NSCLC datasets and NSCLC cells, exploring its links with clinical outcomes, tumor immunity, and autophagy genes through bioinformatics analysis after transcriptome sequencing of RBBP4‐knockdown and control PC9 cells. We identified differentially expressed genes (DEGs) and conducted Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway enrichment, and protein–protein interaction network analyses. The significance of autophagy‐related DEGs was evaluated for diagnosis and prognosis using the GSE30219 dataset. Experiments both in vivo and in vitro explored the biological mechanisms behind RBBP4‐mediated autophagic cell death in NSCLC. Results: RBBP4 overexpression in NSCLC correlates with a poorer prognosis. Eighteen types of immune cell were significantly enriched in cultures that had low RBBP4 expression compared high expression. DEGs associated with RBBP4 are enriched in autophagy pathways. Transcriptomic profiling of the PC9 cell line identified autophagy‐related DEGs associated with RBBP4 that exhibited differential expression in NSCLC, suggesting prognostic applications. In vitro experiments demonstrated that RBBP4 knockdown induced autophagy and apoptosis in PC9 cells, promoting cell death, which was inhibited by 3‐MA. In vivo, targeted siRNA against RBBP4 significantly reduced tumor development in PC9 cell‐injected nude mice, elevating autophagy‐related protein levels and inducing apoptosis and necrosis in tumor tissues. Conclusion: In NSCLC, RBBP4 upregulation correlates with poor prognosis and altered immunity. Its knockdown induces autophagic cell death in NSCLC cells. These results indicate RBBP4 as a potential NSCLC diagnostic marker and its autophagy modulation as a prospective therapeutic target. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is a leading cause of cancerrelated mortality worldwide, necessitating improved diagnostic and prognostic markers. Immunohistochemical (IHC) markers such as alpha-fetoprotein (AFP), glypican-3 (GPC3), heat shock protein 70 (HSP70), and cytokeratin 19 (CK19) have shown promise in HCC detection and prognosis. However, their utility in clinical practice remains to be fully elucidated. Materials and Methods: We conducted a retrospective study analyzing 129 HCC tissue samples for the expression of AFP, GPC3, HSP70, and CK19 using IHC staining. Clinicopathological parameters, including tumor size, grade, presence of cirrhosis, and patient survival, were correlated with marker expression. Survival analysis was performed using Kaplan-Meier curves and log-rank tests. Results: Our analysis revealed variable expression patterns for AFP, GPC3, HSP70, and CK19 in HCC tissues. AFP and GPC3 exhibited moderate to high expression levels, while HSP70 showed moderate expression, and CK19 demonstrated lower expression. Positive correlations were observed between marker expression and tumor size, grade, and the presence of cirrhosis (p < 0.05). Additionally, higher expression levels of AFP, GPC3, and HSP70 were associated with shorter overall survival and lower survival rates at 1 year and 3 years (p < 0.001). In contrast, lower expression levels of CK19 were associated with better overall survival and higher survival rates. Conclusion: Our study highlights the diagnostic and prognostic potential of AFP, GPC3, HSP70, and CK19 in HCC. These markers exhibit distinct expression patterns and associations with clinicopathological parameters and patient outcomes, underscoring their utility in guiding clinical management decisions. Further validation studies in larger cohorts are warranted to confirm our findings and facilitate the integration of these markers into routine clinical practice. [ABSTRACT FROM AUTHOR]

Background: Tumor morphology, immune function, inflammatory levels, and nutritional status play critical roles in the progression of intrahepatic cholangiocarcinoma (ICC). This multicenter study aimed to investigate the association between markers related to tumor morphology, immune function, inflammatory levels, and nutritional status with the prognosis of ICC patients. Additionally, a novel tumor morphology immune inflammatory nutritional score (TIIN score), integrating these factors was constructed. Methods: A retrospective analysis was performed on 418 patients who underwent radical surgical resection and had postoperative pathological confirmation of ICC between January 2016 and January 2020 at three medical centers. The cohort was divided into a training set (n = 272) and a validation set (n = 146). The prognostic significance of 16 relevant markers was assessed, and the TIIN score was derived using LASSO regression. Subsequently, the TIIN-nomogram models for OS and RFS were developed based on the TIIN score and the results of multivariate analysis. The predictive performance of the TIIN-nomogram models was evaluated using ROC survival curves, calibration curves, and clinical decision curve analysis (DCA). Results: The TIIN score, derived from albumin-to-alkaline phosphatase ratio (AAPR), albumin–globulin ratio (AGR), monocyte-to-lymphocyte ratio (MLR), and tumor burden score (TBS), effectively categorized patients into high-risk and low-risk groups using the optimal cutoff value. Compared to individual metrics, the TIIN score demonstrated superior predictive value for both OS and RFS. Furthermore, the TIIN score exhibited strong associations with clinical indicators including obstructive jaundice, CEA, CA19-9, Child–pugh grade, perineural invasion, and 8th edition AJCC N stage. Univariate and multivariate analysis confirmed the TIIN score as an independent risk factor for postoperative OS and RFS in ICC patients (p < 0.05). Notably, the TIIN-nomogram models for OS and RFS, constructed based on the multivariate analysis and incorporating the TIIN score, demonstrated excellent predictive ability for postoperative survival in ICC patients. Conclusion: The development and validation of the TIIN score, a comprehensive composite index incorporating tumor morphology, immune function, inflammatory level, and nutritional status, significantly contribute to the prognostic assessment of ICC patients. Furthermore, the successful application of the TIIN-nomogram prediction model underscores its potential as a valuable tool in guiding individualized treatment strategies for ICC patients. These findings emphasize the importance of personalized approaches in improving the clinical management and outcomes of ICC. [ABSTRACT FROM AUTHOR]

Background: Recently, increasing data have suggested that the lncRNA small nucleolar RNA host genes (SNHGs) were aberrantly expressed in hepatocellular carcinoma (HCC), but the association between the prognosis of HCC and their expression remained unclear. The purpose of this meta‐analysis was to determine the prognostic significance of lncRNA SNHGs in HCC. Methods: We systematically searched Embase, Web of Science, PubMed, and Cochrane Library for eligible articles published up to February 2024. The prognostic significance of SNHGs in HCC was evaluated by hazard ratios (HRs) and 95% confidence intervals (CIs). Odds ratios (ORs) were used to assess the clinicopathological features of SNHGs. Results: This analysis comprised a total of 25 studies covering 2314 patients with HCC. The findings demonstrated that over‐expressed SNHGs were associated with larger tumor size, multiple tumor numbers, poor histologic grade, earlier lymphatic metastasis, vein invasion, advanced tumor stage, portal vein tumor thrombosis (PVTT), and higher alpha‐fetoprotein (AFP) level, but not with hepatitis B virus (HBV) infection, and cirrhosis. In terms of prognosis, patients with higher SNHG expression were more likely to have shorter overall survival (OS), relapse‐free survival (RFS), and disease‐free survival (DFS). Conclusions: In conclusion, upregulation of SNHGs expression correlates with shorter OS, RFS, DFS, tumor size and numbers, histologic grade, lymphatic metastasis, vein invasion, tumor stage, PVTT, and AFP level, suggesting that SNHGs may serve as prognostic biomarkers in HCC. [ABSTRACT FROM AUTHOR]

Background: It is unclear whether the systemic inflammation response index (SIRI) can predict the prognosis of patients with hepatocellular carcinoma (HCC). Consequently, the present study focused on systematically identifying the relationship between SIRI and the prognosis of patients with HCC through a meta-analysis. Methods: Systematic and comprehensive studies were retrieved from PubMed, Web of Science, Embase, and the Cochrane Library from their inception to August 10, 2023. The role of SIRI in predicting overall survival (OS) and progression-free survival (PFS) in HCC was determined using pooled hazard ratios (HRs) and 95% confidence intervals (CIs). Odds ratios (ORs) and 95% CIs were pooled to analyze the correlations between SIRI and the clinicopathological features of HCC. Results: Ten articles involving 2,439 patients were included. An elevated SIRI was significantly associated with dismal OS (HR=1.75, 95% CI=1.52-2.01, p<0.001) and inferior PFS (HR=1.66, 95% CI=1.34-2.05, p<0.001) in patients with HCC. Additionally, according to the combined results, the increased SIRI was significantly related to multiple tumor numbers (OR=1.42, 95% CI=1.09-1.85, p=0.009) and maximum tumor diameter >5 cm (OR=3.06, 95% CI=1.76-5.30, p<0.001). However, the SIRI did not show any significant relationship with sex, alpha-fetoprotein content, Child-Pugh class, or hepatitis B virus infection. Conclusion: According to our results, elevated SIRI significantly predicted OS and PFS in patients with HCC. Moreover, the SIRI was significantly associated with tumor aggressiveness. [ABSTRACT FROM AUTHOR]

Esophageal cancer (EC) is an aggressive malignancy with a poor prognosis. Various factors, including dietary habits, and antacid and antibiotic use, have been shown to influence the esophageal microbiome. Conversely, enrichment and diversity of the esophageal microbiome can also impact its function. Recent studies have revealed prevalent changes in the esophageal microbiome among patients with EC, thus suggesting the potential contribution of the esophageal microbiome to EC development. Additionally, distinct microbiome compositions have been observed in patients with different responses to radiotherapy and chemotherapy, indicating the role of the esophageal microbiome in modulating treatment outcomes. In this review, we have examined previous studies on the esophageal microbiome in healthy individuals and patients with EC or other esophageal diseases, with a focus on identifying microbial communities associated with EC pathogenesis and prognosis. Understanding the role of the microbiome in EC may aid in early detection and optimized treatment strategies, ultimately leading to better outcomes for patients. [ABSTRACT FROM AUTHOR]

Background: There is very limited evidence on biomarkers for evaluating the clinical behavior and therapeutic response in rectal cancer (RC) with positive expression of cancer stem cells (CSCs). Methods: An exploratory prospective study was conducted, which included fresh samples of tumor tissue from 109 patients diagnosed with primary RC. Sociodemographic, pathological and clinical characteristics were collected from medical records and survey. The OCT4 protein was isolated using the Western Blot technique. It was calculated the DCEA, DOCT4, and DOCT4/GUSB values by assessing the changes before and after chemotherapy, aiming to evaluate the therapeutic response. Results: Patients had an average age of 69.9 years, with 55% (n=60) being male. Approximately 63.3% of the tumors were undifferentiated, and the most frequent staging classification was pathological stage III (n=64; 58.7%). Initial positive expression was observed in 77.1% of the patients (n=84), and the median DCEA was -1.03 (-3.82 - 0.84) ng/ml, with elevated levels (< -0.94 ng/ml) found in 51.4% of the subjects (n=56). Being OCT4 positive and having an elevated DCEA value were significantly associated with undifferentiated tumor phenotype (p=0.002), advanced tumor progression stage (p <0.001), and negative values of DOCT4 (p <0.001) (suggestive of poor therapeutic response) compared to those without this status. Conclusion: This study identified a significant and directly proportional association among the values of DCEA, DOCT4, and DOCT4/GUSB. These findings suggest that DCEA holds potential as a clinical biomarker for determining the undifferentiated tumor phenotype, advanced clinical stage, and poor therapeutic response in RC with CSCs positive expression. [ABSTRACT FROM AUTHOR]

Tumor mutation burden (TMB) level is identified as a useful predictor in multiple tumors including colon adenocarcinoma (COAD). However, the function of TMB related genes has not been explored previously. In this study, we obtained patients' expression and clinical data from The Cancer Genome Atlas (TCGA) and the National Center for Biotechnology Information (NCBI). TMB genes were screened and subjected to differential expression analysis. Univariate Cox and LASSO analyses were utilized to construct the prognostic signature. The efficiency of the signature was tested by using a receiver operating characteristic (ROC) curve. A nomogram was further plotted to assess the overall survival (OS) time of patients with COAD. In addition, we compared the predictive performance of our signature with other four published signatures. Functional analyses indicated that patients in the low-risk group have obviously different enrichment of tumor related pathways and tumor infiltrating immune cells from that of high-risk patients. Our findings suggested that the ten genes' prognostic signature could exert undeniable prognostic functions in patients with COAD, which might provide significant clues for the development of personalized management of these patients. [ABSTRACT FROM AUTHOR]

Selection of patients undergoing liver resection for HCC in cirrhotic livers Treatment allocation In patients with HCC in a cirrhotic liver, resection candidates are selected based on liver function, tumour stage and performance status [[11], [17]]. Additional tumour tissue biomarkers in patients undergoing liver resection Regarding biomarkers measured in tumour tissue, PD-L1 expression in tumour or intra-tumoural inflammatory cells was related to tumour aggressiveness [[126]] and predicted recurrence [[127]]. CHAPTER 2: SELECTION OF PATIENTS UNDERGOING LIVER TRANSPLANTATION FOR HCC Current selection criteria for transplantation of patients with HCC In patients undergoing liver transplantation for HCC, survival should be comparable to those with benign indications [[27]]. Transplantation of patients with HCC in non-cirrhotic livers In contrast to patients with liver cirrhosis and HCC, no selection criteria have been established for patients with HCC in non-cirrhotic livers. [Extracted from the article]

Background: To assess the prognostic role of gamma‐glutamyl transpeptidase to lymphocyte count ratio (GLR) and develop a prognostic nomogram for patients with oral cancer. Methods: A prospective cohort (n = 1011) was conducted during July 2002 to March 2021 in Southeastern China. Results: The median follow‐up time was 3.5 years. Multivariate Cox regression (OS: HR = 1.51, 95% CI: 1.04, 2.18) and Fine–Gray model (DSS: HR = 1.68, 95% CI: 1.14, 2.49) both showed that high GLR could act as an indicator of poor prognosis. A nonlinear dose–response relationship was observed between continuous GLR and the risk of all‐cause mortality (p for overall = 0.028, p for nonlinear = 0.048). Compare with TNM stage, time‐dependent ROC curve proved that GLR‐based nomogram model performs better in predicting prognosis (the area under curve for 1‐, 3‐, and 5‐years mortality: 0.63, 0.65, and 0.64 vs. 0.76, 0.77, and 0.78, p < 0.001). Conclusion: GLR might be a useful tool in predicting prognosis for patients with oral cancer. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) has a high incidence and mortality worldwide, which seriously threatens people's physical and mental health. Coagulation is closely related to the occurrence and development of HCC. Whether coagulation-related genes (CRGs) can be used as prognostic markers for HCC remains to be investigated. Methods : Firstly, we identified differentially expressed coagulation-related genes of HCC and control samples in the datasets GSE54236, GSE102079, TCGA-LIHC, and Genecards database. Then, univariate Cox regression analysis, LASSO regression analysis, and multivariate Cox regression analysis were used to determine the key CRGs and establish the coagulation-related risk score (CRRS) prognostic model in the TCGA-LIHC dataset. The predictive capability of the CRRS model was evaluated by Kaplan–Meier survival analysis and ROC analysis. External validation was performed in the ICGC-LIRI-JP dataset. Besides, combining risk score and age, gender, grade, and stage, a nomogram was constructed to quantify the survival probability. We further analyzed the correlation between risk score and functional enrichment, pathway, and tumor immune microenvironment. Results: We identified 5 key CRGs (FLVCR1, CENPE, LCAT, CYP2C9, and NQO1) and constructed the CRRS prognostic model. The overall survival (OS) of the high-risk group was shorter than that of the low-risk group. The AUC values for 1 -, 3 -, and 5-year OS in the TCGA dataset were 0.769, 0.691, and 0.674, respectively. The Cox analysis showed that CRRS was an independent prognostic factor for HCC. A nomogram established with risk score, age, gender, grade, and stage, has a better prognostic value for HCC patients. In the high-risk group, CD4+T cells memory resting, NK cells activated, and B cells naive were significantly lower. The expression levels of immune checkpoint genes in the high-risk group were generally higher than that in the low-risk group. Conclusions: The CRRS model has reliable predictive value for the prognosis of HCC patients. [ABSTRACT FROM AUTHOR]

Aim: Few studies have followed the effects of red blood cell (RBC) transfusion on patient outcomes throughout the disease course in lung cancer. The aim of our study was to evaluate the relationship between blood transfusion frequency and disease prognosis in lung cancer patients receiving chemotherapy, to review the complications experienced and our clinical practices. Methods: This study was conducted as an observational study between 01.07.2021 and 31.12.2021. Patients diagnosed with small-cell lung cancer were included in the study. Patient data were collected retrospectively. During the follow-up period, patients who received and did not receive blood transfusions were compared in terms of various clinical conditions. Results: A total of 405 patients were included. Blood transfusion was performed in 96 (23.7%) patients. While the rate of infection development was 68.8% in the transfused group, this rate was statistically significantly lower at 35.3% in the non-transfused group (p<0.001). The median progression rate was statistically significantly higher in the group with infection (p=0.001). It was determined that 21 (38.2%) patients who resulted in exitus were transfused with an average of 3.1±3.0 units, and an average of 2.81±2.24 units of blood was transfused to 75 (21.4%) of the 350 (86.4%) surviving patients. A statistically significant difference was found between whether blood transfusion was performed in surviving and non-survived patients (p=0.011). Conclusions: It was determined that RBC transfusions during the disease in patients with lung cancer patients who underwent chemotherapy may adversely affect survival and disease progression. [ABSTRACT FROM AUTHOR]

Background: Inflammation is implicated in tumorigenesis and has been reported as an important prognostic factor in cancers. In this study, we aimed to develop and validate a novel inflammation score (IFS) system based on 12 inflammatory markers and explore its impact on intrahepatic cholangiocarcinoma (ICC) survival after hepatectomy. Methods: Clinical data of 446 ICC patients undergoing surgical treatment were collected from the Primary Liver Cancer Big Data, and then served as a training cohort to establish the IFS. Furthermore, an internal validation cohort including 175 patients was used as internal validation cohort of the IFS. A survival tree analysis was used to divide ICC patients into three groups (low-, median-, and high- IFS-score groups) according to different IFS values. Kaplan-Meier (KM) curves were used to compare the overall survival (OS) and recurrence-free survival (RFS) rates among three different groups. Cox regression analyses were applied to explore the independent risk factors influencing OS and RFS. Results: In the training cohort, 149 patients were in the low-IFS-score group, 187 in the median-IFS-score group, and 110 in the high-IFS-score group. KM curves showed that the high-IFS-score group had worse OS and RFS rates than those of the low- and median-IFS-score groups (P < 0.001) in both the training and validation cohorts. Moreover, multivariable Cox analyses identified high IFS as an independent risk factor for OS and RFS in the training cohort. The area under the curve values for OS prediction of IFS were 0.703 and 0.664 in the training and validation cohorts, respectively, which were higher than those of the American Joint Committee on Cancer (AJCC) 7th edition TNM stage, AJCC 8th edition TNM stage, and the Child-Pugh score. Conclusion: Our results revealed the IFS was an independent risk factor for OS and RFS in patients with ICC after hepatectomy and could serve as an effective prognostic prediction system in daily clinical practice. [ABSTRACT FROM AUTHOR]

Background: Pediatric liver transplantation is an important modality for treating biliary atresia. The overall survival (OS) rate of pediatric liver transplantation has significantly improved compared with that of 20 years ago, but it is still unsatisfactory. The anesthesia strategy of maintaining low central venous pressure (CVP) has shown a positive effect on prognosis in adult liver transplantation. However, this relationship remains unclear in pediatric liver transplantation. Thus, this study was conducted to review the data of pediatric living-donor liver transplantation to analyze the associations of different CVP levels with the prognosis of recipients. Methods: This was a retrospective study and the patients were divided into two groups according to CVP levels after abdominal closure: low CVP (LCVP) (≤ 10 cmH2O, n = 470) and high CVP (HCVP) (> 10 cmH2O, n = 242). The primary outcome measured in the study was the overall survival rate. The secondary outcomes included the duration of mechanical ventilation in the intensive care unit (ICU), length of stay in the ICU, and postoperative stay in the hospital. Patient demographic and perioperative data were collected and compared between the two groups. Kaplan-Meier curves were constructed to determine the associations of different CVP levels with the survival rate. Results: In the study, 712 patients, including 470 in the LCVP group and 242 in the HCVP group, were enrolled. After propensity score matching, 212 pairs remained in the group. The LCVP group showed a higher overall survival rate than the HCVP group in the Kaplan-Meier curves and multivariate Cox regression analyses (P = 0.018), and the HCVP group had a hazard ratio of 2.445 (95% confidence interval, 1.163–5.140). Conclusion: This study confirmed that a low-CVP level at the end of surgery is associated with improved overall survival and a shorter length of hospital stay. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality worldwide. It is a highly heterogeneous disease with poor prognosis and limited treatment options, which highlights the need for reliable biomarkers. This study aims to explore molecular markers that allow stratification of HCC and may lead to better prognosis and treatment prediction. Materials and methods: We studied 20 candidate genes (HCC hub genes, potential drug target genes, predominant somatic mutant genes) retrieved from literature and public databases with potential to be used as the molecular markers. We analysed expression of the genes by RT-qPCR in 30 HCC tumour and adjacent non-tumour paired samples from Vietnamese patients. Fold changes in expression were then determined using the 2−∆∆CT method, and unsupervised hierarchical clustering was generated using Cluster v3.0 software. Results: Clustering of expression data revealed two subtypes of tumours (proliferative and normal-like) and four clusters for genes. The expression profiles of the genes TOP2A, CDK1, BIRC5, GPC3, IGF2, and AFP were strongly correlated. Proliferative tumours were characterized by high expression of the c-MET, ARID1A, CTNNB1, RAF1, LGR5, and GLUL1 genes. TOP2A, CDK1, and BIRC5 HCC hub genes were highly expressed (> twofold) in 90% (27/30), 83% (25/30), and 83% (24/30) in the tissue samples, respectively. Among the drug target genes, high expression was observed in the GPC3, IGF2 and c-MET genes in 77% (23/30), 63% (19/30), and 37% (11/30), respectively. The somatic mutant Wnt/ß-catenin genes (CTNNB1, GLUL and LGR5) and TERT were highly expressed in 40% and 33% of HCCs, respectively. Among the HCC marker genes, a higher percentage of tumours showed GPC3 expression compared to AFP expression [73% (23/30) vs. 43% (13/30)]. Conclusion: The custom panel and molecular markers from this study may be useful for diagnosis, prognosis, biomarker-guided clinical trial design, and prediction of treatment outcomes. [ABSTRACT FROM AUTHOR]

Objective To summarize the clinical features of optic neuritis (ON) complicated with chronic hepatitis B virus (HBV) infection, and evaluate the effectiveness of different treatment regimens, recurrence of ON, visual prognosis, HBV reactivation, liver function and liver structure changes. Methods and Results Total 19 patients (23 eyes) with acute ON complicated with chronic HBV infection admitted to Beijing Tongren Hospital, Capital Medical University from January 2015 to June 2021 were included. There were 13 females and 6 males, 15 cases with monocular onset, 17 cases with unidirectional course of disease, and 6 cases with optic disc edema. The time to the worst visual acuity (peak time) was 3 (2, 7) d after onset, and 16/23 eyes had severe visual impairment. Enhanced MRI showed abnormal intensity in orbital, intraductal or intracranial segments of optic nerve, even involving optic nerve sheath and optic chiasm. Anti-nuclear antibody (ANA) was positive in 5 cases and A type Sjögren's syndrome antibody (SSA) was weakly positive in one case. Cerebrospinal fluid (CBF) pressure decreased in 1/7 cases and white blood cell count increased in 2/7 cases. HBV DNA positive group (HBV DNA ≥ 100 IU/ml, 10 cases and 11 eyes) had more severe visual impairment than negative group (HBV DNA < 100 IU/ml, 9 cases and 12 eyes), the difference was statistically significant (Fisher's exact probability: P = 0.005, 0.003). HBV DNA positive group was treated with entecavir, and the recurrence of ON was ignored during follow-up. HBV DNA negative group didn't receive antiviral therapy, one case progressed to cirrhosis, 3 cases had abnormal liver function, and 2 cases had HBV reactivation. Conclusions The visual function of patients with ON complicated with chronic HBV infection was seriously impaired, and the response to glucocorticoid therapy was not good. The visual impairment of patients with positive HBV DNA was more serious than patients with negative HBV DNA. Patients with ON complicated with chronic HBV infection should be treated with antiviral drugs in combination with glucocorticoid therapy. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is one of the most malignant tumors to threaten human life, and the survival rate remains low due to delayed diagnosis. Meanwhile, lncRNAs have great potential for application in tumor prognosis, therefore relevant research in hepatocellular carcinoma is indispensable.Methods: Based on the EZH2 expression, the differentially expressed lncRNAs DElncRNAs), miRNAs (DEmiRNAs), and mRNAs (DEmRNAs) were identified in hepatocellular carcinoma by using the TCGA database. Bioinformatics technology was utilized to determine the effect of key genes in HCC progression. The methylation and immune infiltration analyses were performed to explore the underlying function of hub genes. Finally, cellular function experiments were performed to investigate the association between identified genes and biological phenotypes in HCC.Results: lncRNA-AC079061.1, hsa-miR-765, and VIPR1 were identified as independent factors that affect the prognosis of hepatocellular carcinoma. The immune infiltration analyses revealed that lncRNA-AC079061.1 can alter the immune microenvironment and thus inhibit the development of HCC by regulating the expression of an immune-related gene (VIPR1). Methylation analyses demonstrated that VIPR1 expression is negatively related to the methylation level in HCC. Experimental results suggested that lncRNA-AC079061.1 and VIPR1 were frequently downregulated in HCC cells, while hsa-miR-765 was significantly upregulated. Moreover, the lncRNA-AC079061.1/VIPR1 axis suppressed the proliferation and invasion of HCC cells.Conclusion: The present study identified the lncRNA-AC079061.1/VIPR1 axis as a novel biomarker that inhibited the proliferation and invasion of hepatocellular carcinoma, affecting the ultimate disease outcome. [ABSTRACT FROM AUTHOR]

Background: As a recognized highly immunogenic tumor, immune checkpoint blockades (ICB) have been widely used as a systemic treatment option for melanoma. However, only about half of treated patients could benefit from it in Caucasians, and only about 15% in Chinese melanoma patients. Robust predictive biomarkers are needed. HHLA2, a new-found member of B7 family, is generally expressed in kinds of tumors, such as melanoma. This study focuses on illustrating the prognostic value of HHLA2 in melanoma immunotherapy and its association with tumor-infiltrating lymphocytes. Methods: HHLA2 expression in pan-cancer and the association with prognosis and immune microenvironment were identified by analyzing gene expression profiles from TCGA database with selected bioinformatics tools and methods. Tumor tissues from 81 cases with advanced and unresectable melanoma were collected for detecting HHLA2 and CD8 levels by immunohistochemistry. Results: HHLA2 was found to be ubiquitously expressed in pan-cancer with high level and correlate with the prognosis of patients. Further comprehensive analysis from TCGA database demonstrated that the highly expressed HHLA2 was remarkably correlated with better prognosis, high infiltration status of various immune-active cells and immune activated pathways in skin cutaneous melanoma (SKCM). Moreover, immunohistochemistry (IHC) analyses of FFPE tissue from melanoma patients revealed that HHLA2 high expression was strongly related to improved response to ICB and indicated a longer progression-free survival (PFS) and overall survival (OS). Besides, HHLA2 expression was found to have a positive association with the density of CD8+ TILs. Conclusion: Our findings revealed that high expression of HHLA2 has important values in predicting the response to ICB and indicating improved PFS and OS in patients with advanced and unresectable melanoma, suggesting that HHLA2 may serve as a costimulatory ligand in melanoma, which renders it as an ideal biomarker for immunotherapy. [ABSTRACT FROM AUTHOR]

Preclinical evidence suggests that gut microbiome regulation may prove to be a new therapeutic target for treating postoperative infection in liver transplant recipients. This review aims to evaluate the most current evidence for the efficacy of probiotics supplementation on postoperative prognosis. The registered through the International prospective register of systematic reviews as CRD42020170379. We searched PubMed, Embase, and Cochrane Library databases for studies published from 1 Jan 1963 to 31 May 2021. The quality of included studies was assessed using the Cochrane risk of bias tool. Study heterogeneity was assessed with the Cochrane Q test and I2 statistic. We applied leave-one-out sensitivity analysis to assess the effect of every single study on the heterogeneity and pooled effect size. Egger's test and observation of funnel plots were used to detecting small-study effects and publication bias. A total of five studies, including 290 patients, were enrolled in the final analysis. Probiotics supplementation resulted in a beneficial outcome both in postoperative infection (RR = 0.199, 95%CI: 0.105 ~ 0.377, p = 0.000), the duration of antibiotic therapy (WMD = 3.031, 95%CI: − 5.905 ~ − 0.157, p = 0.039), and the length of hospital stay (SMD = − 0.274, 95%CI: − 0.530 ~ − 0.018, p = 0.036). The main effective infection types were urinary tract infection (RR = 0.176, 95%CI: 0.063 ~ 0.496, p = 0.001) and intraabdominal infection (RR = 0.225, 95%CI: 0.084 ~ 0.607, p = 0.003), but not pneumonia infection (RR = 0.301, 95%CI: 0.076 ~ 1.203, p = 0.089). There were no statistically significant differences for the intensive care unit stay (WMD = − 0.752, 95%CI: − 1.819 ~ − 0.315, p = 0.167) and postoperative mortality (RR = 0.794, 95%CI: 0.210 ~ 3.008, p = 0.734) in the two groups. Probiotics supplementation as an effective assistant treatment for reducing postoperative infection rates, the duration of antibiotic therapy, and the length of hospital stay after liver transplantation has application prospects. [ABSTRACT FROM AUTHOR]

Objective: The purpose of the current study was to evaluate the association between C-reactive protein-to-platelet ratio (CPR), neutrophil-to-lymphocyte*platelet ratio (NLPR) and fibrinogen-to-platelet ratio (FPR) and the prognoses of pyogenic liver abscess (PLA) patients.Methods: A cohort of 372 patients with confirmed PLA were enrolled in this retrospective study between 2015 and 2021. Laboratory data were collected on admission within 24 h. The demographic characteristics and clinical features were recorded. Risk factors for outcomes of PLA patients were determined via multivariate logistic regression analyses, and optimal cut-off values were estimated by using the receiver operating characteristic (ROC) curve analysis.Results: Out of 372 patients, 57.8% were men, 80 (21.5%) developed sepsis, and 33 (8.9%) developed septic shock. The levels of CPR, NLPR and FPR were significantly increased in the development of sepsis, and prolonged hospital stays in PLA patients. The multivariate logistic regression analysis indicated that the CPR (OR: 2.262, 95% CI: 1.586-3.226, p < 0.001), NLPR (OR: 1.118, 95% CI: 1.070-1.167, p < 0.001) and FPR (OR: 1.197, 95% CI: 1.079-1.329, p = 0.001) were independent risks of PLA patients with sepsis, and NLPR (OR: 1.019, 95% CI: 1.004-1.046, p = 0.019) was shown to be an independent predictor of prolonged hospital stays. The ROC curve results showed that the three biomarkers had different predictive values, and CPR proved to work best, with a ROC value of 0.851 (95% CI: 0.807-0.896, p < 0.001) for sepsis.Conclusion: Higher levels of CPR, NLPR and FPR were associated with a higher risk of poor outcomes. Moreover, a high CPR level performed best when predicting the clinical outcome in PLA patients. [ABSTRACT FROM AUTHOR]

Cholangiocarcinoma (CCA) is the second most common primary liver cancer and associated with a dismal prognosis due to the lack of an efficient systemic therapy. In contrast to other cancers, new immunotherapies have demonstrated unsatisfactory results in clinical trials, underlining the importance of a deeper understanding of the special tumor microenvironment of CCA and the role of immune cells interacting with the tumor. Tumor-infiltrating lymphocytes (TILs) are an important component of the adaptive immune system and the foundation of current immunotherapy. Therefore, the aim of this systemic review is to summarize the current literature focusing on the proportions and distribution, molecular pathogenesis, prognostic significance of TILs and their role in immunotherapy for CCA patients. In CCA, CD8+ and CD4+ T lymphocytes represent the majority of TILs and are mostly sequestered around the cancer cells. CD20+ B lymphocytes and Natural Killer (NK) cells are less frequent. In contrast, Foxp3+ cells (regulatory T cells, Tregs) are observed to infiltrate into the tumor. In the immune microenvironment of CCA, cancer cells and stromal cells such as TAMs, TANs, MSDCs and CAFs inhibit the immune protection function of TILs by secreting factors like IL-10 and TGF-β. With respect to molecular pathogenesis, the Wnt/-catenin, TGF-signaling routes, aPKC-i/P-Sp1/Snail Signaling, B7-H1/PD-1Pathway and Fas/FasL signaling pathways are connected to the malignant potential and contributed to tumor immune evasion by increasing TIL apoptosis. Distinct subtypes of TILs show different prognostic implications for the long-term outcome in CCA. Although there are occasionally conflicting results, CD8+ and CD4+ T cells, and CD20+ B cells are positively correlated with the oncological prognosis of CCA, while a high number of Tregs is very likely associated with worse overall survival. TILs also play a major role in immunotherapy for CCA. In summary, the presence of TILs may represent an important marker for the prognosis and a potential target for novel therapy, but more clinical and translational data is needed to fully unravel the importance of TILs in the treatment of CCA. [ABSTRACT FROM AUTHOR]

Background: We explored the relationship between the platelet-lymphocyte ratio (PLR), the prognostic nutritional index (PNI), the lactate dehydrogenase-albumin ratio (LDH/albumin ratio; LAR), the controlling nutritional status (CONUT) score, and the long-term survival of colon cancer patients. Methods: We conducted a retrospective analysis of the clinical data and follow-up materials of 126 patients with colon cancer who underwent surgical treatment in the Department of Gastrointestinal Surgery of Jiangnan University Affiliated Hospital from June 2012 to December 2015. The receiver operating characteristic curve (ROC) was used to distinguish the high ratio group from the low ratio group. The Kaplan Meier method was used to draw the survival curve in our survival analysis. The log rank test was used for the univariate analysis and the Cox multivariate regression analysis was used to analyze the correlation between preoperative PLR, PNI, LAR, conut scores, and overall survival (OS) and progression free survival (PFS) of patients with colon cancer. Results: The median follow-up time was 72 months. The OS rates at 3 and 5 years were 83.3% and 78.5%, respectively. The PFS rates at 3 and 5 years were 79.3% and 77.6%, respectively. The 3-year and 5-year OS rates in the low LAR group (=4.91) were 90.9% and 87.1%, respectively, and were 56.0% and 44.0% in the high LAR group (>4.91) respectively. Univariate and multivariate analyses showed that the LAR value was correlated with OS and PFS (P < 0.05). Conclusion: A high preoperative LAR is an independent predictor of the prognosis of colon cancer patients. [ABSTRACT FROM AUTHOR]

Background: Acute-on-chronic liver failure (ACLF) is featured with rapid deterioration of chronic liver disease and poor short-term prognosis. Liver transplantation (LT) is recognized as the curative option for ACLF. However, there is no standard in the prediction of the short-term survival among ACLF patients following LT.Method: Preoperative data of 132 ACLF patients receiving LT at our center were investigated retrospectively. Cox regression was performed to determine the risk factors for short-term survival among ACLF patients following LT. Five conventional score systems (the MELD score, ABIC, CLIF-C OFs, CLIF-SOFAs and CLIF-C ACLFs) in forecasting short-term survival were estimated through the receiver operating characteristic (ROC). Four machine-learning (ML) models, including support vector machine (SVM), logistic regression (LR), multi-layer perceptron (MLP) and random forest (RF), were also established for short-term survival prediction.Results: Cox regression analysis demonstrated that creatinine (Cr) and international normalized ratio (INR) were the two independent predictors for short-term survival among ACLF patients following LT. The ROC curves showed that the area under the curve (AUC) ML models was much larger than that of conventional models in predicting short-term survival. Among conventional models the model for end stage liver disease (MELD) score had the highest AUC (0.704), while among ML models the RF model yielded the largest AUC (0.940).Conclusion: Compared with the traditional methods, the ML models showed good performance in the prediction of short-term prognosis among ACLF patients following LT and the RF model perform the best. It is promising to optimize organ allocation and promote transplant survival based on the prediction of ML models. [ABSTRACT FROM AUTHOR]

Background: Cell division cycle-associated (CDCA) gene family is essential to cell cycle regulation. Numerous studies have illuminated that dysfunction of CDCA genes may not only lead to uncontrolled cell proliferation resulting in tumorigenesis but also influence immune cell infiltration in tumors. However, the role of the CDCA gene family on the prognosis and immune infiltration in nasopharyngeal carcinoma (NPC) remains to be unclear. Methods: SBC human ceRNA array V1.0 was used to measure mRNA expression in three pairs of NPC tissues and nasopharyngitis tissues. The expression of CDCA8 was confirmed in an IHC microarray containing 130 NPC patients. Two external GEO cohorts were enrolled for further analysis. Prognosis analysis was performed using the Kaplan–Meier method. Gene set enrichment analysis (GSEA) was applied to explore the potential mechanism of CDCA genes in NPC. The relationship between CDCA gene family and immune infiltration in NPC was evaluated using the Xcell tool. Results: CDCA genes were broadly upregulated in NPC tissues compared to nasopharyngitis tissues, and high expression of CDCA3/5/8 indicated worse prognosis in NPC. Besides cell cycle pathways, we found that CDCA3/5/8 were involved in multiple immune-related pathways. Overexpression of CDCA8 was strongly associated with less infiltration of CD8+ T cells and more infiltration of CD4+ Th1 cells and was negatively correlated with immune checkpoint blockade (ICB)-related genes. Conclusion: CDCA gene family was upregulated in NPC, and their expressions were associated with adverse prognosis. High expression of CDCA8 was associated not only with poor prognosis, but also with less immune infiltration and downregulation of ICB-related genes in NPC. [ABSTRACT FROM AUTHOR]

Background: Bladder cancer (BC) is a common urinary tract system tumor with high recurrence rate and different populations show distinct response to immunotherapy. Novel biomarkers that can accurately predict prognosis and therapeutic responses are urgently needed. Here, we aim to identify a novel prognostic and therapeutic responses immune-related gene signature of BC through a comprehensive bioinformatics analysis. Methods: The robust rank aggregation was conducted to integrate differently expressed genes (DEGs) in datasets of the Cancer Genome Atlas (TCGA) and the gene expression omnibus (GEO). Lasso and Cox regression analyses were performed to formulate a novel mRNA signature that could predict prognosis of BC patients. Subsequently, the prognostic value and predictive value of the signature was validated with two independent cohorts GSE13507 and IMvigor210. Finally, quantitative Real-time PCR (qRT-PCR) analysis was conducted to determine the expression of mRNAs in BC cell lines (UM-UC-3, EJ-1, SW780 and T24). Results: We built a signature comprised the eight mRNAs: CNKSR1, COPZ2, CXorf57, FASN, PCOLCE2, RGS1, SPINT1 and TPST1. Our prognostic signature could be used to stratify BC population into two risk groups with distinct immune profile and responsiveness to immunotherapy. The results of qRT-PCR demonstrated that the eight mRNAs exhibited different expression levels in BC cell lines. Conclusion: Our study constructed a convenient and reliable 8-mRNA gene signature, which might provide prognostic prediction and aid treatment decision making of BC patients in clinical practice. [ABSTRACT FROM AUTHOR]

Cancer as one of the most common causes of death has always been one of the major health challenges globally. Since, the identification of tumors in the early tumor stages can significantly reduce mortality rates; it is required to introduce novel early detection tumor markers. MicroRNAs (miRNAs) have pivotal roles in regulation of cell proliferation, migration, apoptosis, and tumor progression. Moreover, due to the higher stability of miRNAs than mRNAs in body fluids, they can be considered as non-invasive diagnostic or prognostic markers in cancer patients. In the present review we have summarized the role of miR-217 during tumor progressions. The miR-217 functions were categorized based on its target molecular mechanisms and signaling pathways. It was observed that miR-217 mainly exerts its function by regulation of the transcription factors during tumor progressions. The WNT, MAPK, and PI3K/AKT signaling pathways were also important molecular targets of miR-217 in different cancers. The present review clarifies the molecular biology of miR-217 and paves the way of introducing miR-217 as a non-invasive diagnostic marker and therapeutic target in cancer therapy. [ABSTRACT FROM AUTHOR]

Background: Bladder cancer (BC) is one of the most common malignancies and has a relatively poor outcome worldwide. In this study, we attempted to construct a novel metabolism-related gene (MRG) signature for predicting the survival probability of BC patients.Methods: First, differentially expressed MRGs between BC and normal samples were identified and used to construct a protein-protein interaction (PPI) network and perform mutation analysis. Next, univariate Cox regression analysis was utilized to select prognostic genes, and multivariate Cox regression analysis was applied to establish an MRG signature for predicting the survival probability of BC patients. Moreover, Kaplan-Meier (KM) survival analysis and receiver operating characteristic (ROC) analysis were performed to evaluate the predictive capability of the MRG signature. Finally, a nomogram based on the MRG signature was established to better predict the survival of BC.Results: In the present study, 27 differentially expressed MRGs were identified, most of which presented mutations in BC patients, and LRP1 showed the highest mutation rate. Next, an MRG signature, including MAOB, FASN and LRP1, was established by using univariate and multivariate Cox regression analysis. Furthermore, survival analysis indicated that BC patients in the high-risk group had a dramatically lower survival probability than those in the low-risk group. Finally, Cox regression analysis showed that the risk score was an independent prognostic factor, and a nomogram integrating age, pathological tumor stage and risk score was established and presented good predictive ability.Conclusion: We successfully constructed a novel MRG signature to predict the prognosis of BC patients, which might contribute to the clinical treatment of BC. [ABSTRACT FROM AUTHOR]

Background: Cholangiocarcinoma (CCA) encompasses a heterogeneous group of malignant tumors with dismal prognosis and increasing incidence worldwide. Both late diagnosis due to the lack of early symptoms and the refractory nature of these tumors seriously compromise patients' welfare and outcomes. Summary: During the last decade, immunotherapy and, more specifically, modulation of immune checkpoints-mediated signaling pathways have been under the spotlight in the field of oncology, emerging as a potential therapeutic approach for the treatment of several cancers, including CCA. Generally, high expression levels of immune checkpoints in patients with CCA have been associated with worse clinical outcomes, particularly with shorter overall survival and relapse-free survival. Thus, immune checkpoint inhibitors (ICIs), which mainly constitute different monoclonal antibodies, have been developed in order to hamper the immune checkpoint-mediated pathways. Interestingly, chemotherapy may increase the expression of immune checkpoints, while other therapeutic approaches such as ablative and targeted therapies may enhance their antitumor activity. In this sense, several clinical trials evaluated the safety and efficacy of ICIs for CCA, both as a monotherapy and in combination with other ICIs or loco-regional and systemic therapies. Additionally, many other clinical trials are currently ongoing and results are eagerly awaited. Here, we summarize the key aspects of immune checkpoint molecules as prognostic factors and therapeutic targets in CCA, highlighting the most recent advances in the field and future research directions. Key Messages: (1) Effective therapeutic approaches for CCA are urgently needed. (2) Expression levels of immune checkpoints in patients with CCA have been proposed to be related with clinical outcomes. (3) Combination of different ICIs may outperform the efficacy of ICI monotherapy for CCA treatment. (4) Recent studies point toward the combination of ICIs and other common therapies, especially chemotherapy, as a promising strategy for treatment of CCA patients. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) were recently implicated in modifying the transforming growth factor β (TGF-β) signaling in multiple cancers. However, TGF-β-derived miRNAs and their potential clinical significance remain largely unexplored in intrahepatic cholangiocarcinoma (ICC). In this study, we proposed an integrated framework that enables the identification of TGF-β-derived miRNAs in ICC (termed "TGFmitor"). A total of 36 TGF-β-derived miRNAs were identified, of which nine significantly correlated with overall survival (OS) and aberrantly expressed in ICC. According to these miRNAs, we discovered and validated a TGF-β associated miRNA signature (TAMIS) in GSE53870 (n =63) and TCGA-CHOL (n =32). To further confirm the clinical interpretation of TAMIS, another validation based on qRT-PCR results from 181 ICC tissues was performed. TAMIS was proven to be an independent risk indicator for both OS and relapse-free survival (RFS). TAMIS also displayed robust performance in three cohorts, with satisfactory AUCs and C-index. Besides, patients with low TAMIS were characterized by superior levels of CD8+ T cells infiltration and PD-L1 expression, while patients with high TAMIS possessed enhanced CMTM6 expression. Kaplan-Meier analysis suggested CMTM6 could further stratify TAMIS. The TAMIShighCMTM6high subtype had the worst prognosis and lowest levels of CD8A and PD-L1 expression relative to the other subtypes, indicating this subtype might behave as "super-cold" tumors. Notably, the improved discrimination was observed when CMTM6 was combined with TAMIS. Overall, our signature could serve as a powerful tool to help improve prognostic management and immunotherapies of ICC patients. [ABSTRACT FROM AUTHOR]

Background: The prognostic nutritional index, a marker of nutritional status and systemic inflammation, is a known biomarker for various cancers. However, few studies have evaluated the predictive value of the prognostic nutritional index in patients with biliary tract cancer. Therefore, we investigated the prognostic significance of the prognostic nutritional index, and developed a risk-stratification system to identify prognostic factors in patients with biliary tract cancer.Methods: Between July 2010 and March 2021, 117 patients with biliary tract cancer were recruited to this single-center, retrospective study. The relationship between clinicopathological variables, including the prognostic nutritional index, and overall survival was analyzed using univariate and multivariate analyses. A P < 0.05 was considered statistically significant.Results: The median age was 75 (range 38-92) years. Thirty patients had intrahepatic cholangiocarcinoma; 29, gallbladder carcinoma; 27, distal cholangiocarcinoma; 17, ampullary carcinoma; and 13, perihilar cholangiocarcinoma. Curative (R0) resection was achieved in 99 patients. In univariate analysis, the prognostic nutritional index (< 42), lymph node metastasis, carbohydrate antigen 19-9 level (> 20 U/mL), preoperative cholangitis, tumor differentiation, operation time (≥ 360 min), and R1-2 resection were significant risk factors for overall survival. The prognostic nutritional index (P = 0.027), lymph node metastasis (P = 0.040), and tumor differentiation (P = 0.006) were independent prognostic factors in multivariate analysis. A combined score of the prognostic nutritional index and pathological findings outperformed each marker alone, in terms of discriminatory power.Conclusions: The prognostic nutritional index, lymph node metastasis, and tumor differentiation were independent prognostic factors after surgical resection in patients with biliary tract cancer. A combined prediction model using the prognostic nutritional index and pathological findings accurately predicted prognosis, and can be used as a novel prognostic factor in patients with biliary tract cancer. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of most prevalent cancer and is a serious healthcare issue worldwide. Portal vein tumor thrombus (PVTT) is a frequent complication and remains as the blockage in the treatment of HCC with high recurrence rate and poor prognosis. There is still no global consensus or standard guideline on the management of HCC with PVTT. In western countries, Sorafenib and Lenvatinib are recommended as the first-line treatment options for HCC patients with PVTT where this condition is now regarded as BCLC Stage C regardless of PVTT types. However, there is growing evidence that supports the close relationship of the extent of PVTT to the prognosis of HCC. Besides the targeted therapy, more aggressive treatment modalities have been proposed and practiced in the clinic which may improve the prognosis of HCC patients with PVTT and prolong the patients' survival time, such as transarterial chemoembolization, radiotherapy, hepatic resection, liver transplantation, and various combination therapies. Herein, we aim to review and summarize the advances in the treatment of HCC with PVTT. [ABSTRACT FROM AUTHOR]

Background: Inflammation and the immune system significantly impact the development, progression, and treatment response of hepatocellular carcinoma (HCC). This retrospective study investigated the neutrophil-to-lymphocyte ratio (NLR) as a prognostic biomarker in Western patients with HCC in the setting of chronic viral hepatitis. Methods: Patients diagnosed with HCC from 2005 to 2016 were selected from a tertiary care institution. NLR was calculated within 30 days prior to treatment and dichotomized at the median. Kaplan–Meier overall survival (OS) curves and Cox hazard proportional models were utilized. Tumor and liver reserve parameters were included in multivariable analyses (MVA). Results: A total of 581 patients met inclusion criteria (median age 61.0 yr; 78.3% male; 66.3% Caucasian) with median OS = 34.9 mo. 371 patients (63.9%) had viral hepatitis, of which 350 had hepatitis C (94.3%). The low-NLR group (

Malignant pleural mesothelioma is an aggressive cancer, heterogeneous in its presentation and behaviour. Despite an increasing knowledge about molecular markers and their diagnostic and prognostic value, they are not used as much as they might be for treatment allocation. It has been recently reported that mesothelioma cells that lack BAP1 (BRCA1 Associated Protein) are sensitive to inhibition of the EZH2 (Enhancer of Zeste Homolog 2) histone methyltransferase. Since we observed strong H3K27me3 (histone H3 lysine 27 trimetylation) immunoreactivity in BAP1 wild-type mesothelioma biopsies, we decided to characterize in vitro the response/resistance of BAP1 wild-type mesothelioma cells to the EZH2 selective inhibitor, EPZ-6438. Here we demonstrate that BAP1 wild-type mesothelioma cells were rendered sensitive to EPZ-6438 upon SIRT1 (Sirtuin 1) silencing/inhibition or when cultured as multicellular spheroids, in which SIRT1 expression was lower compared to cells grown in monolayers. Notably, treatment of spheroids with EPZ-6438 abolished H3K27me3 and induced the expression of CDKN2A (Cyclin-Dependent Kinase Inhibitor 2A), causing cell growth arrest. EPZ-6438 treatment also resulted in a rapid and sustained induction of the genes encoding HIF2α (Hypoxia Inducible Factor 2α), TG2 (Transglutaminase 2) and IL-6 (Interleukin 6). Loss of CDKN2 is a common event in mesothelioma. CDKN2A silencing in combination with EPZ-6438 treatment induced apoptotic death in mesothelioma spheroids. In a CDKN2A wild-type setting apoptosis was induced by combining EPZ-6438 with 1-155, a TG2 selective and irreversible inhibitor. In conclusion, our data suggests that the expression of CDKN2A predicts cell fate in response to EZH2 inhibition and could potentially stratify tumors likely to undergo apoptosis. [ABSTRACT FROM AUTHOR]

Background & aims: Pyogenic liver abscesses (PLA) are space‐occupying lesions in the liver that produce high morbidity and mortality. The clinical characteristics and prognosis of abscesses is different depending on the bacterial culture results and require different strategies for management. The aim of this study was to investigate the clinical characteristics and prognostic factors of patients with PLA. Methods: Clinical features, laboratory tests and etiology of PLA between 2006 to 2011 and 2012 to 2017 in a single hospital were retrospectively reviewed. The incidence and mortality of PLA caused by Escherichia coli and Klebsiella pneumoniae were compared and the risk factors for multiple organ dysfunction (MODS) and endophthalmitis were evaluated. Results: Among the 1,572 PLA patients, the proportion with PLA increased from 333 (21.2%) in 2006‐2011 to 1,239 (78.8%) in 2012‐2017 without any investigation and treatment procedure differences. K pneumoniae was the main isolate in analysed pus cultures (85.6%). The mortality rate of patients with K pneumoniae infection was lower in the latter period (6.7% vs 0.7%, P =.035). Multivariate analyses revealed that age, fever, MODS and length of hospital stay were factors affecting poor prognosis (death + unhealed/uncured) in PLA patients after treatment and that cardiovascular disease, pleural effusion and pulmonary infection were risk factors for MODS, while diabetes mellitus was the only risk factor for endophthalmitis. Most patients (95.5%) with PLA recovered after abscess drainage/puncture and antibiotic therapy. Conclusions: Pleural effusion, fever, MODS and length of hospital stays were factors useful in predicting PLA outcomes. [ABSTRACT FROM AUTHOR]

Background: Although criteria for liver transplantation, such as the Milan criteria and Hangzhou experiences, have become popular, criteria to guide adjuvant therapy for patients with hepatocellular carcinoma after liver transplantation are lacking.Methods: We collected data from all consecutive patients from 2012 to 2019 at three liver transplantation centers in China retrospectively. Univariate and multivariate analyses were used to analyze preoperative parameters, such as demographic and clinical data. Using data obtained in our center, calibration curves and the concordance Harrell's C-indices were used to establish the final model. The validation cohort comprised the patients from the other centers.Results: Data from 233 patients were used to construct the nomogram. The validation cohort comprised 36 patients. Independent predictors of overall survival (OS) were identified as HbeAg positive (P = 0.044), blood-type compatibility unmatched (P = 0.034), liver transplantation criteria (P = 0.003), and high MELD score (P = 0.037). For the validation cohort, to predict OS, the C-index of the nomogram was 0.874. Based on the model, patients could be assigned into low-risk (≥ 50%), intermediate-risk (30-50%), and high-risk (≤ 30%) groups to guide adjuvant therapy after surgery and to facilitate personalized management.Conclusions: The OS in patients with hepatocellular carcinoma after liver transplantation could be accurately predicted using the developed nomogram. [ABSTRACT FROM AUTHOR]

Background/aims: This study aimed to investigate the factors associated with prolonged hospital stay and in-hospital mortality in patients with pyogenic liver abscess.Methods: We retrospectively reviewed data from patients with pyogenic liver abscess who were admitted between 2005 and 2018 at three tertiary hospitals in Jeonbuk province, South Korea. Prolonged hospital stay was defined as a duration of hospital admission of more than 21 days.Results: A total of 648 patients (406 men and 242 women) diagnosed with pyogenic liver abscess were enrolled in the study. The mean maximal diameter of the liver abscess was 5.4 ± 2.6 cm, and 74.9% of the lesions were single. The three groups were divided according to the maximal diameter of the abscess. Laboratory parameters indicated a more severe inflammatory state and higher incidence of complications and extrahepatic manifestations with increasing abscess size. Rates of percutaneous catheter drainage (PCD) insertion, multiple PCD drainage, and salvage procedures as well as duration of drainage were also higher in the large liver abscess group. Of note, the duration of hospitalization and in-hospital mortality were significantly higher in the large hepatic abscess group. A multivariate analysis revealed that underlying diabetes mellitus, hypoalbuminemia, high baseline high-sensitivity C-reactive protein (hs-CRP) and procalcitonin levels, and large maximal abscess diameter were independent factors associated with prolonged hospital stay. Regarding in-hospital mortality, acute kidney injury at admission and maximal diameter of the abscess were independent factors associated with in-hospital mortality.Conclusions: A large maximal diameter of the liver abscess at admission indicated prolonged hospitalization and poor prognosis. More aggressive treatment strategies with careful monitoring are warranted in patients with large liver abscesses. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is a highly recurrent tumor after resection and has been closely related to hypoxia. Hypoxia-inducible factors 1α and 2α (HIF-1α and HIF-2α) have been shown to contribute to tumor progression and therapy resistance in HCC. We evaluated the prognostic and clinicopathological significance of HIF-1α and HIF-2α in HCC patients. Methods: We systematically searched Embase, Cochrane, PubMed, Scopus and Web of Science (WOS) from inception to 1 June 2020 for studies evaluating HIF-1α and/or HIF-2α expression in HCC. Selected articles evaluate at least one factor by immunohistochemistry (IHC) in HCC patients who underwent surgical resection, and its relationship with prognosis and/or clinicopathological features. Study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CDR42020191977). We meta-analyzed the data extracted or estimated according to the Parmar method employing STATA software. We evaluated the overall effect size for the hazard ratio (HR) and odds ratio (OR) with 95% confidence interval (CI), as well as heterogeneity across studies with the I 2 statistic and chi-square-based Q test. Moreover, we conducted subgroup analysis when heterogeneity was substantial. Publication bias was assessed by funnel plot asymmetry and Egger's test. Results: HIF-1α overexpression was correlated with overall survival (OS), disease-free survival (DFS)/recurrence-free survival (RFS) and clinicopathological features including Barcelona Clinic Liver Cancer (BCLC), capsule infiltration, intrahepatic metastasis, lymph node metastasis, tumor–node–metastasis (TNM), tumor differentiation, tumor number, tumor size (3 cm), vascular invasion and vasculogenic mimicry. We also detected a possible correlation of HIF-1α with alpha-fetoprotein (AFP), cirrhosis, histological grade, tumor size (5 cm) and albumin after subgroup analysis. Initially, only DFS/RFS appeared to be associated with HIF-2α overexpression. Subgroup analysis denoted that HIF-2α overexpression was related to OS and capsule infiltration. Conclusions: HIF-1α and HIF-2α overexpression is related to poor OS, DFS/RFS and some clinicopathological features of HCC patients, suggesting that both factors could be useful HCC biomarkers. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) accounts for one of the leading causes of cancer-related death, and is attributed to the dysregulation of genes involved in genome stability. DDX11, a DNA helicase, has been implicated in rare genetic disease and human cancers. Yet, its clinical value, biological function, and the underlying mechanism in HCC progression are not fully understood. Here, we show that DDX11 is upregulated in HCC and exhibits oncogenic activity via EZH2/p21 signaling. High expression of DDX11 is significantly correlated with poor outcomes of HCC patients in two independent cohorts. DDX11 overexpression increases HCC cell viabilities and colony formation, whereas DDX11 knockdown arrests cells at G1 phase without alteration of p53 expression. Ectopic expression of DDX11 reduces, while depletion of DDX11 induces the expression of p21. Treatment of p21 siRNA markedly attenuates the cell growth suppression caused by DDX11 silence. Further studies reveal that DDX11 interacts with EZH2 in HCC cells to protect it from ubiquitination-mediated protein degradation, consequently resulting in the downregulation of p21. In addition, E2F1 is identified as one of the upstream regulators of DDX11, and forms a positive feedback loop with EZH2 to upregulate DDX11 and facilitate cell proliferation. Collectively, our data suggest DDX11 as a promising prognostic factor and an oncogene in HCC via a E2F1/DDX11/EZH2 positive feedback loop. [ABSTRACT FROM AUTHOR]

The function of microRNA-27a (miR-27a) expression in cholangiocarcinoma (CCA) remains largely unclear; therefore, this study aimed to investigate the clinical significance and functional role of miR-27a in CCA. This study included 117 paired CCA tissues and adjacent normal tissues from CCA patients who received surgical resection. Reverse transcription-quantitative polymerase chain reaction was used to measure the expression levels of miR-27a in CCA tissues and cell lines. A Kaplan–Meier curve and Cox regression analysis were used to determine overall prognostic performance. The effects of miR-27a on cell proliferation, migration, and invasion were measured by CCK-8 and Transwell assays. The expression levels of miR-27a in patients with CCA and cell lines were higher than those in adjacent normal tissues and normal cells, respectively. Additionally, miR-27a levels were found to be associated with lymph node metastasis and TNM stages. The overall survival time of CCA patients with high miR-27a expression was poorer than that of those with low miR-27a expression. Furthermore, miR-27a overexpression promoted CCA cell proliferation, migration, and invasion, whereas knockdown of miR-27a suppressed cell proliferation, migration, and invasion. Taken together, these results suggest the potential usefulness of miR-27a in the prognosis and progression of CCA. [ABSTRACT FROM AUTHOR]

Background: Leucine aminopeptidases (LAPs) have been reported to be involved in tumor cell proliferation, invasion and angiogenesis. However, the relationship between serum leucine aminopeptidases and prognosis of hepatocellular carcinoma (HCC) patients who underwent liver transplantation (LT) was not yet reported. We aimed to evaluate the prognostic value of preoperative serum leucine aminopeptidases in these patients. Methods: Clinical data of 106 HCC patients who underwent LT were retrospectively analyzed. The sex ratio, age, HBV infection, Child–Pugh stage, preoperative tumor therapy, AFP, the largest tumor size, tumor number, Edmondson grading, macro- and micro-vascular invasion of patients with different serum LAP level and compositions of patients who met the criteria of Milan, UCSF or Hangzhou were compared using the chi-square test. The Kaplan–Meier method was performed in survival analysis and the log rank test was used in survival comparison. Results: Serum LAPs were correlated with alpha-fetoprotein (AFP), the largest tumor size, tumor number and macro-vascular invasion. Patients with serum LAPs > 87 U/L showed significantly poorer disease-free survival (DFS) and overall survival (OS) than those with serum LAPs ≤ 87 U/L. Univariate analysis indicated that serum LAPs, AFP, the largest tumor size, tumor number, and macro- and micro-vascular invasion were all associated with DFS and OS. Multivariate analysis showed that serum LAPs, macro-vascular invasion and the largest tumor size were independently correlated with DFS and OS. Serum LAPs could also distinguish prognosis between patients with different status of AFP, the largest tumor size, tumor number, and macro- and micro-vascular invasion, as well as patients within and beyond selection criteria, such as Milan, University of California, San Francisco and Hangzhou criteria. Conclusion: Elevated preoperative serum LAPs were associated with advanced tumor stage and aggressive biological behavior, and thus a poor outcome, which could be a prognostic marker for HCC patients who underwent LT. [ABSTRACT FROM AUTHOR]

Endocrine therapy is the main treatment option for estrogen receptor-positive (ER+) breast cancer (BC). Compared with other clinical subtypes, ER+ BC patients usually have a more favorable prognosis. However, almost all ER+ BCpatients develop endocrine resistance and disease progression eventually. A large number of studies based on liquid biopsy suggest that ESR1 mutations may play a key role in this process. For patients with ER+ metastatic BC (MBC), ESR1 is an important prognostic factor and may associate with the resistance to endocrine therapy, like aromatase inhibitors. The advances of sequencing technologies allow us to conduct longitudinal monitoring of disease and unveil the clinical implications of each ESR1 sub-clone in ER+ MBC. Moreover, since the ESR1 -related endocrine resistance has not been fully addressed by existing agents, more potent cornerstone drugs should be developed as soon as possible. Herein, we reviewed the recent progress of detecting ESR1 mutations based on liquid biopsy and different sequencing technologies in ER+ MBC and discussed its clinical impacts and prospects. [ABSTRACT FROM AUTHOR]

Clear cell renal cell carcinoma (ccRCC) has an unpredictable clinical consequence even with the use of usual prognostic factors. To determine whether utilization of cell proliferation and cell adhesion by using MCM2 and CD44 immuno-expression could predict the biological performance of ccRCC. MCM2 and CD44 protein expression levels in tumor tissues from 120 ccRCC patients were evaluated by immunohistochemistry. The relationships between MCM2 and CD44 expression and clinicopathological parameters were evaluated. The overall survival (OS) was computed by the Kaplan-Meier method. The role of MCM2 and CD44 in the prognosis was estimated by univariate and multivariate Cox regressions. The results showed high MCM2 and CD44 protein expression levels in 63.3% and 55% of ccRCC cases, respectively. MCM2 and CD44 over-expression was significantly related to tumor grade (p = 0.001 and p = 0.003, respectively), T stage (p = 0.005 and p = 0.008, respectively), lymph node status (p = 0.015 and p = 0.040, respectively), AJCC stage (p = 0.000 and p = 0.002, respectively) and OS (p = 0.019 and p = 0.001, respectively). Multivariate Cox regression showed that high MCM2 and CD44 expression levels were independently associated with prognosis of ccRCC cases (HR = 2.687, 2.810, 95% CI: 1.217-5.920, 1.267-6.233, respectively). MCM2 and CD44 are considered as independent risk and poor prognostic factors for the prognosis of ccRCC patients. [ABSTRACT FROM AUTHOR]

Purpose: Mounting studies have investigated the clinicopathological and prognostic value of hypoxia-inducible factor-1α (HIF-1α) in breast cancer (BC), yet conclusions remain controversial. Therefore, we conducted this meta-analysis to clarify this issue. Methods: All relevant studies were searched using Cochrane Library, Web of Science, PubMed, and EMBASE online databases. Pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were applied to evaluate the clinicopathological and prognostic value of HIF-1α, respectively. Subgroup analysis and sensitivity analysis were performed to investigate heterogeneity and stability of the results. Begg's funnel plot and Egger's test were used to examine publication bias. Results: A total of 31 eligible studies including 5177 subjects were enrolled. Of these, 25 studies assessed the prognostic role of HIF-1α and included 4546 individuals. Twenty-three studies involving 3277 individuals evaluated the clinicopathological significance of HIF-1α. High expression level of HIF-1α was correlated with poor overall survival (OS) (HR = 1.59, 95% CI = 1.40–1.80, P < 0.001), disease-free survival (DFS) (HR = 1.87, 95% CI = 1.53–2.28, P < 0.001), relapse-free survival (HR = 1.36, 95% CI = 1.07–1.73, P = 0.001), and cancer-specific survival (HR = 1.55, 95% CI = 1.10–2.19, P = 0.012). Pooled data from studies using multivariate survival analysis also showed that HIF-1α expression was associated with worse OS (HR = 1.59, 95% CI = 1.32–1.92, P < 0.001) and DFS (HR = 1.60, 95% CI = 1.39–1.84, P < 0.001). Additionally, high HIF-1α expression was associated with advanced tumor–node–metastasis stage, positive lymph-node status, negative ER status, ductal type, advanced histologic grade, high Ki67 expression, and strong VEGF expression. Conclusion: HIF-1α might serve as an independent prognostic biomarker and a promising therapeutic target for BC. Future large-scale prospective randomized trials are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

Aim: The study aimed to investigate the clinical significance of preoperative alpha-fetoprotein (AFP) and gamma-glutamyl transferase (GGT) (A-G score) on hepatocellular carcinoma (HCC) patients. Methods: A total of 474 solitary HCC patients were included. Survival analysis was evaluated by Kaplan-Meier method. Prognostic factors were analyzed in a multivariate model. The comparison of the predictive value of AFP, GGT, and A-G score was performed by receiver operating characteristic curve (ROC) analysis and decision curve analysis (DCA). Results: Of the 474 patients, 137(28.9%), 241(50.8%), and 96(20.3%) patients were assigned to A-G score 0, 1, and 2, respectively. In multivariate analysis, A-G score, tumor size, microvascular invasion, tumor differentiation, satellite lesion, and state of HBV infection were independently predictive factors for RFS of solitary HCC patients. The A-G score could significantly stratify solitary HCC patients with a distinguished prognosis. The 1-, 3-, and 5-year RFS and OS among patients with A-G score 1 was better than that of patients with A-G score 2 and worse than that of patients with A-G score 0(all p < 0.05). Based on the result from the ROC analysis and DCA analysis, the A-G score appeared to be superior to either AFP or GGT alone in the prediction of prognosis of solitary HCC patients. In the subgroup analysis, the A-G score could accurately predict the prognosis of solitary HCC patients without MVI or with liver cirrhosis. Conclusions: Preoperative A-G score could effectively and simply predict prognosis of solitary HCC patients after hepatectomy, especially for those with non-MVI solitary HCC or those with liver cirrhosis. [ABSTRACT FROM AUTHOR]

The present study analyzed the ability of metabolic burden indices from 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) to predict tumor recurrence following orthotopic liver transplantation (OLT) in patients with hepatocellular carcinoma (HCC). Seven major metabolic indices were measured by 18F-FDG PET/CT in 93 patients with HCC, prior to OLT. The Mann-Whitney U test was then used to predict the association of metabolic indices, including the maximum standardized uptake value (SUVmax), tumor-to-mediastinum SUV ratio, tumor-to-normal-liver SUV ratio, SUV normalized to lean body mass metabolic tumor volume (MTV), total lesion glycolysis (TLG) and uptake-volume product (UVP), with the recurrence risk. The Deauville-like scoring system was used to quantify the recurrence risk. Univariate and multivariable Cox regression models were performed to determine survival rate. The results showed that Deauville-like score (PET-negative vs. -positive), MTV (cutoff value, 13.36), TLG (cutoff value, 62.21) and UVP (cutoff value, 66.60) had high prediction performance for tumor recurrence (P<0.05). TLG had the highest receiver operating characteristics area under the curve of 0.725. Among the clinical factors, high level of α-fetoprotein (AFP, ≥144 ng/ml), Milan criteria, tumor number (>3), involvement of both right and left lobes, and tumor size (>5 cm) were found to be significant predictors of tumor recurrence. Patients in the low metabolic group had longer recurrence-free survival (RFS) times compared with those in the high metabolic group, regardless of whether they met the Milan criteria or not. AFP, uptake-volume product according the SUV mean of mediastinum (UVP-M), Milan criteria, lymph node metastasis, and the number of tumors were significant prognostic factors for RFS (P<0.05) in both univariate and multivariate survival analyses. Additionally, the MVI was a significant prognostic factor based on univariate survival analyses. Overall, the present study demonstrated the metabolic burden indices measured by PET/CT, Deauville-like score, MTV, TLG and UVP as significant prognostic factors in patients with HCC following OLT. The combination of metabolic indices measured by PET/CT and the existing criteria, such as the Milan criteria, may play an important role in evaluating the suitability of OLT in specific patients. [ABSTRACT FROM AUTHOR]

Summary: Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) is a significant clinical problem associated with poor surgical outcomes. This study aims to summarize the current evidence on risk prediction models of HCC recurrence after LT. PubMed and EMBASE were searched to May 25, 2019, for relevant articles. Studies originally designed to develop or validate a risk prediction model for HCC recurrence after LT were included. Two independent authors summarized the study characteristics and evaluated the risk of bias and applicability concerns in the included studies. From 26 included studies, 18 original risk prediction models were determined, but only five models were externally validated. The average number of predictors involved in the construction of risk models was three. The most frequently employed predictors were alpha‐fetoprotein, tumor size, vascular invasion, tumor number, tumor differentiation, and neutrophil‐lymphocyte ratio. Most studies showed good discriminatory performance (AUC >0.75). The overall quality of the included studies was generally low. Most of the original models lacked the highly recommended external and prospective validation in diverse populations. The AFP model was the well‐validated preoperative risk model that can stratify patients into high‐ and low‐risk groups. [ABSTRACT FROM AUTHOR]